Disentangling the relative importance of T cell responses in COVID-19: leading actors or supporting cast?

Stephen J. Kent, David S. Khoury, Arnold Reynaldi, Jennifer A. Juno, Adam K. Wheatley, Eva Stadler, E. John Wherry, James Triccas, Sarah C. Sasson, Deborah Cromer, Miles P. Davenport

Research output: Contribution to journalArticleResearchpeer-review

78 Citations (Scopus)


The rapid development of multiple vaccines providing strong protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a major achievement. There is now compelling evidence for the role of neutralizing antibodies in protective immunity. T cells may play a role in resolution of primary SARS-CoV-2 infection, and there is a widely expressed view that T cell-mediated immunity also plays an important role in vaccine-mediated protection. Here we discuss the role of vaccine-induced T cells in two distinct stages of infection: firstly, in protection from acquisition of symptomatic SARS-CoV-2 infection following exposure; secondly, if infection does occur, the potential for T cells to reduce the risk of developing severe COVID-19. We describe several lines of evidence that argue against a direct impact of vaccine-induced memory T cells in preventing symptomatic SARS-CoV-2 infection. However, the contribution of T cell immunity in reducing the severity of infection, particularly in infection with SARS-CoV-2 variants, remains to be determined. A detailed understanding of the role of T cells in COVID-19 is critical for next-generation vaccine design and development. Here we discuss the challenges in determining a causal relationship between vaccine-induced T cell immunity and protection from COVID-19 and propose an approach to gather the necessary evidence to clarify any role for vaccine-induced T cell memory in protection from severe COVID-19.

Original languageEnglish
Pages (from-to)387-397
Number of pages11
JournalNature Reviews Immunology
Issue number6
Publication statusPublished - Jun 2022

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